POS0237 MAJOR ADVERSE CARDIOVASCULAR EVENTS, MALIGNANCIES AND VENOUS THROMBOEMBOLISM BY BASELINE CARDIOVASCULAR RISK: A POST HOC ANALYSIS OF ORAL SURVEILLANCE
Authors: M. H. Buch, C. Charles-Schoeman, J. Curtis, M. Dougados, D. L. Bhatt, J. T. Giles, S. R. Ytterberg, G. G. Koch, I. Vranic, J. Wu, C. Wang, K. Kwok, S. Menon, J. L. Rivas, A. Yndestad, C. A. Connell, Z. Szekanecz
Journal: Annals of the Rheumatic Diseases (2022)

Background ORAL Surveillance was a post-authorisation safety study of tofacitinib vs TNF inhibitors (TNFi) in rheumatoid arthritis (RA) patients (pts) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor and an inadequate response to methotrexate (MTX). CV disease has overlapping risk factors with malignancies and venous thromboembolism (VTE), including older age, smoking, hypertension and diabetes. 1,2 Objectives To evaluate the impact of pts’ baseline (BL) CV risk on the incidence and risk of major adverse CV events (MACE), malignancies and VTE in ORAL Surveillance. Methods Pts on stable MTX were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID) or a TNFi (adalimumab 40 mg every 2 weeks or etanercept 50 mg once weekly). Incidence rates (IRs; pts with first events/100 pt-yrs) and hazard ratios (HRs; tofacitinib vs TNFi) were evaluated for adjudicated MACE (defined as CV death [excluding CV death due to pulmonary embolism (PE)], non-fatal MI and non-fatal stroke), malignancies (excluding NMSC) and VTE (including fatal/non-fatal deep vein thrombosis and PE). Across safety outcomes, IRs/HRs were stratified by BL CV risk score: pts were first categorised by history of coronary artery disease (HxCAD); pts without a HxCAD were further stratified by BL CV risk score categories (high [≥20%], intermediate [≥7.5–&lt;20%], borderline [≥5–&lt;7.5%] and low [&lt;5%] risk), with a 1.5 multiplier applied per EULAR recommendations. 3 Results 4362 pts were included: tofacitinib 5 mg BID, n=1455; tofacitinib 10 mg BID, n=1456; TNFi, n=1451. In these treatment groups, during a median follow-up of 4.0 yrs, MACE was reported in 47 (3.2%), 51 (3.5%) and 37 (2.6%) pts, malignancies in 62 (4.3%), 60 (4.1%) and 42 (2.9%) pts, and VTE in 17 (1.2%), 34 (2.3%) and 10 (0.7%) pts, respectively. Approximately two-thirds of pts had intermediate to high CV risk, or HxCAD, and risk was well-balanced across treatment groups (Table 1). Across treatments, MACE and malignancies IRs were highest in pts with a HxCAD or a high BL CV risk score (Figure 1). IRs/HRs for MACE, malignancies and VTE were generally higher with tofacitinib vs TNFi. Differences between tofacitinib vs TNFi in MACE and malignancy IRs/HRs were typically more pronounced in pts with a HxCAD or at least intermediate BL CV risk score, and less so in pts with lower BL CV risk score (Figure 1). In tofacitinib 10 mg BID-treated pts, VTE IRs/HRs (vs TNFi) were clearly highest in pts with a HxCAD or high BL CV risk score; no association between VTE and BL CV risk scores was observed with tofacitinib 5 mg BID or TNFi (Figure 1). Table 1. Percentages of pts with a HxCAD and pts without a HxCAD categorised by BL CV risk scores, per ASCVD-PCE risk calculator 4 with a 1.5 multiplier applied 3 Tofacitinib 5 mg BID (N=1455) Tofacitinib 10 mg BID (N=1456) TNFi (N=1451) HxCAD, n (% ) 161 (11.1) 172 (11.8) 164 (11.3) No HxCAD: BL CV risk score, per ASCVD-PCE risk calculator, n (% ) High (≥20%) 274 (18.8) 303 (20.8) 296 (20.4) Intermediate (≥7.5–&lt;20%) 490 (33.7) 516 (35.4) 505 (34.8) Borderline (≥5–&lt;7.5%) 200 (13.7) 174 (12.0) 155 (10.7) Low (&lt;5%) 313 (21.5) 272 (18.7) 315 (21.7) Missing data 17 (1.2) 19 (1.3) 16 (1.1) HxCAD is defined as any history of MI, coronary heart disease, stable angina pectoris or coronary artery procedures n, number of pts with specified characteristics; N, number of evaluable pts Conclusion In this post hoc analysis of data from ORAL Surveillance, IRs for MACE and malignancies (excluding NMSC) were highest across treatments, and increased with both tofacitinib doses vs TNFi, in pts with a HxCAD or high BL CV risk score; a similar finding was observed for VTE IRs in pts treated with tofacitinib 10 mg BID. These findings support recommendations to regularly assess and address CV risk in RA pts. References [1]Koene et al. Circulation 2016; 133: 1104-1114. [2]Ageno et al. Circulation 2008; 117: 93-102. [3]Agca et al. Ann Rheum Dis 2017; 76: 17-28. [4]American College of Cardiology, American Heart Association. ASCVD risk estimator. https://tools.acc.org/ldl/ascvd_risk_estimator/index.html# !/calulate/estimator/. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by Tanya Guha, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Eli Lilly, Gilead Sciences, MSD, Pfizer Inc and Roche, Grant/research support from: Pfizer Inc, Roche and UCB, Christina Charles-Schoeman Consultant of: AbbVie, Gilead Sciences, Pfizer Inc and Sanofi-Regeneron, Grant/research support from: AbbVie, Bristol-Myers Squibb and Pfizer Inc, Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, CorEvitas, Eli Lilly, Janssen, Myriad, Pfizer Inc, Roche/Genentech and UCB, Grant/research support from: Amgen, CorEvitas, Crescendo Bio and Pfizer Inc, Maxime Dougados Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Deepak L Bhatt Grant/research support from: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Eli Lilly, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Medtronic, MyoKardia, Novo Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic and The Medicines Company, Jon T Giles Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Genentech, Gilead Sciences and UCB, Grant/research support from: Pfizer Inc, Steven R. Ytterberg Consultant of: Corbus Pharmaceuticals, Kezar Life Sciences and Pfizer Inc, Gary G Koch Shareholder of: IQVIA, Grant/research support from: AbbVie, Acceleron, Amgen, Arena, AstraZeneca, Cytokinetics, Eli Lilly, Gilead Sciences, GSK, Huya Bioscience International, Johnson &amp; Johnson, Landos Biopharma, Merck, Momentum, Novartis, Otsuka, Pfizer Inc, Sanofi and vTv Therapeutics, Employee of: University of North Carolina at Chapel Hill, Ivana Vranic Shareholder of: Pfizer Inc, Employee of: Pfizer Ltd, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Kenneth Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Sujatha Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose L. Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer SLU, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Carol A. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Zoltán Szekanecz Speakers bureau: AbbVie, Eli Lily, Novartis, Pfizer Inc, Roche and Sanofi, Paid instructor for: AbbVie, Eli Lilly, Gedeon Richter, Novartis, Pfizer Inc and Roche, Consultant of: AbbVie, Eli Lily, Novartis, Pfizer Inc, Roche and Sanofi